Gene Expression Profiling of Human Adrenocortical Tumors Using Complementary Deoxyribonucleic Acid Microarrays Identifies Several Candidate Genes as Markers of Malignancy
Florence de Fraipont,
Michelle El Atifi,
Nadia Cherradi,
Gwennaelle Le Moigne,
Geneviève Defaye,
Rémi Houlgatte,
Jérôme Bertherat,
Xavier Bertagna,
Pierre-François Plouin,
Eric Baudin,
François Berger,
Christine Gicquel,
Olivier Chabre and
Jean-Jacques Feige
Institut National de la Santé et de la Recherche Médicale, Equipe Mixte 01-05, Department of Cell Regulation and Dynamics, Commissariat à l’Energie Atomique (F.d.F., G.L.M., G.D., O.C., J.-J.F.), 38054 Grenoble, France; Departments of Integrative Biology (F.d.F.) and Endocrinology (O.C.) and Transcriptome Analysis Platform, Genopole Rhône-Alpes (M.E.A., F.B.), University Hospital of Grenoble, 38043 Grenoble, France; COMETE: The French Network for Studies on Human Adrenal Cortical and Medullary Tumors (F.d.F., N.C., G.L.M., G.D., J.B., X.B., P.-F.P., E.B., C.G., O.C., J.-J.F.), European Hospital Georges Pompidou, 75908 Paris, France; Institut National de la Santé et de la Recherche Médicale, Equipe de Recherche Méthodologique 02-06, University of Méditerranée (R.H.), 13288 Marseille, France; Department of Endocrinology, Cochin Hospital (J.B., X.B.), 75014 Paris, France; Department of Hypertension, European Hospital Georges Pompidou (P.-F.P.), 75908 Paris, France; Department of Endocrine Cancerology, Gustave-Roussy Institute (E.B.), 94805 Villejuif, France; and Laboratory of Functional Endocrine Explorations, Trousseau Hospital (C.G.), 75571 Paris, France
Address all correspondence and requests for reprints to: Dr. Jean-Jacques Feige, Institut National de la Santé et de la Recherche Médicale, Equipe Mixte 01-05, Department of Cellular Responses and Dynamics, Angiogenesis Laboratory, Commissariat à l’Energie Atomique Grenoble, 17 rue des Martyrs, F-38054 Grenoble Cedex 9, France. E-mail: jjfeige{at}cea.fr.
The aim of this study was to identify predictor sets of geneswhose over- or underexpression in human sporadic adrenocorticaltumors would help to identify malignant vs. benign tumors andto predict postsurgical metastatic recurrence. For this, weanalyzed the expression of 230 candidate genes using cDNA microarraysin a series of 57 well-characterized human sporadic adrenocorticaltumors (33 adenomas and 24 carcinomas). We identified two clustersof genes (the IGF-II cluster containing eight genes, includingIGF-II, and the steroidogenesis cluster containing six genesencoding steroidogenic enzymes plus eight other genes) whosecombined levels of expression appeared to be good predictorsof malignancy. This predictive value was as strong as that ofthe pathological score of Weiss. The analysis of the populationof carcinomas (13 tumors) for genes whose expression would bestrongly different between recurring and nonrecurring tumorsallowed identification of 14 genes meeting these criteria. Amongthese genes, there are probably new markers of tumor evolutionthat will deserve additional validation on a larger scale. Takentogether, these results show that the parallel analysis of theexpression levels of a selected group of genes on microgramquantities of tumor RNA (a quantity that can be obtained fromfine needle aspirations) appears as a complementary method tohistopathology for the diagnosis and prognosis of evolutionof adrenocortical carcinomas.
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